Coach Charlie Strong said Harris was injured in practice Thursday.
Harris tore his right ACL in December and had been attempting to fully recover in time for the season opener against Kentucky on Sept. 2. The sophomore from Miami was the team's second-leading receiver last season with 37 catches for 455 yards and two touchdowns.
A favorite target for high school teammate and current Cardinals quarterback Teddy Bridgewater, Harris had been expected to be one of Louisville's starting receivers. It is his fourth knee injury while at Louisville.
Strong says Harris "provides so much energy to the team."